How does durvalumab impact the treatment of unresectable stage III non-small cell lung cancer based on previous treatment?

This study looked at the outcomes of durvalumab (Imfinzi) in patients with unresectable (cannot be surgically removed) stage 3 non-small cell lung cancer (NSCLC) who received different combinations of chemoradiotherapy (CRT) previously. The authors found that the use of durvalumab improved survival in all patients previously treated with CRT.

NSCLC accounts for 85% of lung cancers found worldwide. The main form of treatment is the surgical removal of tumors plus CRT. Tumors that cannot be removed surgically can be difficult to treat. Patients with unresectable tumors often have a poorer prognosis. 

Some cancers have on their surface a protein called PD-L1. This protein blocks the immune system's function so the cancer can grow undetected. Durvalumab is an immunotherapy that blocks the PD-L1 protein. Therefore it helps the immune system to detect and attack the cancer. It was shown previously that durvalumab improves the outcomes of patients with unresectable NSCLC. However, whether the type of previous therapy affected these outcomes is not clear. 

A total of 709 patients with unresectable NSCLC were included in this study. All patients had previously received CRT. 473 patients received treatment with durvalumab. 236 patients received treatment with a placebo. The outcomes of patients were analyzed based on the previous treatment variables such as platinum-based or other types of chemotherapy, small (below 60 Gy), medium (60-66 Gy), or large (over 66 Gy) doses of radiotherapy, the amount of time from CRT until durvalumab/placebo treatment (less or more than 14 days) and use of other treatments before CRT. The average length of follow-up was 25.2 months.

Overall, durvalumab treatment was associated with a significant increase in survival without cancer worsening  (by 48%) compared to placebo. This benefit, ranging from 37% to 66% was seen in all CRT subgroups. Durvalumab also improved overall survival in all subgroups (by 14% to 65%) compared to placebo.

The response to treatment was significantly higher in the durvalumab group (28.4%) compared to placebo (16%) in most groups. The response to treatment was similar between the durvalumab and placebo groups in patients who received small radiotherapy doses (17.6% vs 20%) and in those who had received chemotherapy before CRT(16.1% vs 13.1%). 

Overall, the percentage of side effects was similar between the durvalumab group (96.8%) and the placebo group (94.9%). This trend was consistent in all CRT subgroups.

The authors concluded that durvalumab improved survival in patients with stage 3 unresectable NSCLC regardless of previous CRT variables. 

This study was funded by AstraZeneca, the manufacturers of durvalumab.